Tumor budding is defined as the presence of single tumor cells or small tumor clusters (less than five cells) that 'bud' from the invasive front of the main tumor. Tumor budding (TB) has recently emerged as an important adverse prognostic factor for many different cancer types. In colorectal carcinoma (CRC), tumor budding has been independently associated with lymph node metastasis and poor outcome. Pathologic assessment of tumor budding by light microscopy requires close evaluation of tumor invasive front on intermediate to high power magnification, entailing locating the 'hotspot' of tumor budding, counting all TB in one high power field, and generating a tumor budding score. By automating these time-consuming tasks, computer-assisted image analysis tools can be helpful for daily pathology practice, since tumor budding reporting is now recommended on select cases. In this paper, we report our work on the development of a tumor budding detection system in CRC from whole-slide Cytokeratin AE1/3 images, based on de novo computer algorithm that automates morphometric analysis of tumor budding.
Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.